STIR: software for tomographic image reconstruction release 2

We present a new version of STIR (Software for Tomographic Image Reconstruction), an open source object-oriented library implemented in C++ for 3D positron emission tomography reconstruction. This library has been designed such that it can be used for many algorithms and scanner geometries, while being portable to various computing platforms. This second release enhances its flexibility and modular design and includes additional features such as Compton scatter simulation, an additional iterative reconstruction algorithm and parametric image reconstruction (both indirect and direct). We discuss the new features in this release and present example results. STIR can be downloaded from http://stir.sourceforge.net

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Signaling of the human P2Y(1) receptor measured by a yeast growth assay with comparisons to assays of phospholipase C and calcium mobilization in 1321N1 human astrocytoma cells

The human P2Y(1) receptor was expressed in the yeast Saccharomyces cerevisiae strain MPY578q5, which is engineered to couple to mammalian G protein-coupled receptors (GPCRs) and requires agonist-induced activation for growth. A range of known P2Y(1) receptor agonists were examined with the yeast growth assay system, and the results were validated by comparing with potencies in the transfected 1321N1 astrocytoma cell line, in which calcium mobilization was measured with a FLIPR (fluorometric-imaging plate reader). The data were also compared with those from phospholipase C activation and radioligand binding with the use of a newly available radioligand [(3)H]MRS2279 (2-chloro-N(6)-methyl-(N)-methanocarba-2’-deoxyadenosine-3’,5’bisphosphate). In the yeast growth assay, the rank order of potency of 2-MeSADP (2-methylthioadenosine 5’-diphosphate), ADP (adenosine 5’-diphosphate), and ATP (adenosine 5’-triphosphate) is the same as those in other assay systems, i.e., 2-MeSADP>ADP>ATP. The P2Y(1)-selective antagonist MRS2179 (N(6)-methyl-2-deoxyadenosine-3’,5’-bisphosphate) was shown to act as an antagonist with similar potency in all systems. The results suggest that the yeast expression system is suitable for screening P2Y(1) receptor ligands, both agonists and antagonists. The yeast system should be useful for random mutagenesis of GPCRs to identify mutants with certain properties, such as selective potency enhancement for small synthetic molecules and constitutive activity

The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds

We extend the effective fragment molecular orbital method (EFMO) into treating fragments connected by covalent bonds. The accuracy of EFMO is compared to FMO and conventional ab initio electronic structure methods for polypeptides including proteins. Errors in energy for RHF and MP2 are within 2 kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides similar to FMO but obtained two to five times faster. For proteins, the errors are also within a few kcal/mol of the FMO results. We developed both the RHF and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip

Behavioral activation interventions for well-being: A meta-analysis

One of the most promising ways to increase well-being is to engage in valued and enjoyable activities. Behavioral activation (BA), an intervention approach most commonly associated with the treatment of depression, is consistent with this recommendation and can easily be adapted for non-clinical populations. This study reports on a meta-analysis of randomized controlled studies to examine the effect of BA on well-being. Twenty studies with a total of 1353 participants were included. The pooled effect size (Hedges's g) indicated that the difference in well-being between BA and control conditions at posttest was 0.52. This significant effect, which is comparable to the pooled effect achieved by positive psychology interventions, was found for non-clinical participants and participants with elevated symptoms of depression. Behavioral activation would seem to provide a ready and attractive intervention for promoting the well-being of a range of populations in both clinical and non-clinical settings

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Recent improvements in the development of A2B adenosine receptor agonists

Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary artery disorders and atherosclerosis

A qualitative synthesis of the positive and negative impacts related to delivery of peer-based health interventions in prison settings

Background Peer interventions involving prisoners in delivering peer education and peer support in a prison setting can address health need and add capacity for health services operating in this setting. This paper reports on a qualitative synthesis conducted as part of a systematic review of prison-based peer interventions. One of the review questions aimed to investigate the positive and negative impacts of delivering peer interventions within prison settings. This covered organisational and process issues relating to peer interventions, including prisoner and staff views. Methods A qualitative synthesis of qualitative and mixed method studies was undertaken. The overall study design comprised a systematic review involving searching, study selection, data extraction and validity assessment. Studies reporting interventions with prisoners or ex-prisoners delivering education or support to prisoners resident in any type of prison or young offender institution, all ages, male and female, were included. A thematic synthesis was undertaken with a subset of studies reporting qualitative data (n=33). This involved free coding of text reporting qualitative findings to develop a set of codes, which were then grouped into thematic categories and mapped back to the review question. Results Themes on process issues and wider impacts were grouped into four thematic categories: peer recruitment training and support; organisational support; prisoner relationships; prison life. There was consistent qualitative evidence on the need for organisational support within the prison to ensure smooth implementation and on managing security risks when prisoners were involved in service delivery. A suite of factors affecting the delivery of peer interventions and the wider organisation of prison life were identified. Alongside reported benefits of peer delivery, some reasons for non-utilisation of services by other prisoners were found. There was weak qualitative evidence on wider impacts on the prison system, including better communication between staff and prisoners. Gaps in evidence were identified. Conclusions The quality of included studies limited the strength of the conclusions. The main conclusion is that peer interventions cannot be seen as independent of prison life and health services need to work in partnership with prison services to deliver peer interventions. More research is needed on long-term impacts